Immune complexes in glomeruli are involved in development of diverse glomerulonephritis. The disposal process of glomerular immune complexes has been unclarified. The present studies were undertaken to determine if thromboxane A
2 (TXA
2) is associated with the disposal of macromolecules in the glomeruli using mice injected with aggregated bovine serum albumin (a-BSA). A-BSA promptly accumulated in the glomeruli, the level reaching a plateau at 6 hr after the injection of a-BSA, and then decreased by 48 hr. The production of glomerular TXA
2, prostaglandin E
2 (PGE
2) and prostaglandin I
2 concomitantly increased with the decrease of a-BSA in the glomeruli. TXA
2 synthase inhibitors and TXA
2 receptor antagonists accelerated clearance of glomerular a-BSA without enhancing renal tissue blood flow. They did not affect a-BSA level in the plasma. In contrast, aminophylline, dopamine and mannitol significantly increased renal tissue blood flow, but did not decrease glomerular a-BSA. TXA
2 synthase inhibitors decreased TXA2 production in the glomeruli. TXA
2 synthase inhibitors and TXA
2 receptor antagonists did not influence the generation of PGE
2. The TXA
2 analogue U-46619 significantly increased the accumulation of a-BSA in the glomeruli. We propose that TXA
2 interferes with the disposal process of aggregated protein in the glomeruli. We also postulate that interception of glomerular activity of TXA
2 may be an effective intervention for managing immune complex-mediated glomerulonephritis and glomerulosclerosis.
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